COLUMBUS, Ohio - Researchers have developed a new way to
use a decade-old imaging method to directly compare the brains of
monkeys with those of humans. Their report appeared in the
journal Science.

The method uses functional
Magnetic Resonance Imaging
(fMRI) - a technique that
measures blood volume and flow
and blood-oxygen levels in the
brain. It also provides an indirect
measure of neuronal activity in
different regions of the brain.

Neurons need oxygen and
glucose to work. Blood carries
both substances, and both can
cross the blood-brain barrier.
When a particular region of the
brain is activated, the blood flow
to that area temporarily increases
in order to supply the neurons with fresh oxygen and glucose.

"What we're doing is an indirect measurement of the human
brain's electrical activity," said Wim Vanduffel, the report's lead
author and an instructor at the Athinoula A. Martinos Center for
Biomedical Imaging in Charlestown, Mass.

"It's the best way at present for
investigating patterns of neural
activity in humans," he said.

The researchers used the same
fMRI technique on humans and
on monkeys to compare activity
in an area of the brain called the
visual cortex, the region that
processes vision and motion.
While each species shares similar
traits in the visual cortex, the
researchers did find distinct
differences between the species
in two key areas.

"Implicit in the neuroscience community was that the monkey
cortex is a good model for the human cortex," said James Todd, a
study co-author and a professor of psychology at Ohio State
University. "Scientists didn't have any choice but to make that
assumption, as the monkey brain was the only model we had to
work with."

What set the fMRI technique used in this study apart from past
fMRI experiments on monkeys is that the monkeys remained
conscious during the experiments.

"Until this point, anybody who has used fMRI on monkeys did so
while the animals were sedated," Todd said. "That presents a real
problem since sedation may alter the patterns of neural activity that
occur when monkeys are awake."

Eleven human subjects each participated in 14 separate fMRI scan
sessions, and three juvenile macaques participated in at least eight
sessions. While each session produced data, some of the sessions
produced weak signals. Therefore, the researchers averaged
together the sessions in order to obtain reliable results.

The experiments were conducted in a laboratory run by Guy
Orban, head of the division of neurophysiolgy at Katholieke
Universiteit Leuven in Belgium, where Wim Vanduffel also holds a
postdoctoral position. Todd was responsible for designing the
images viewed by all of the subjects.

For each session, a human subject lay on his back inside the fMRI
and watched as nine randomly connected lines began to rotate on
a monitor inside the machine. This procedure could not be used on
the monkeys, however, because monkeys don't like lying on their
backs. Instead, the researchers used juvenile monkeys that could
be seated within the fMRI apparatus.

The researchers looked for areas of the visual cortex that were
activated while the subjects watched rotating 3-D images. Each
portion of a subject's visual cortex was scanned during each
session in the fMRI. In order to better see the areas of activity in
the monkey brain, the macaques were injected with a solution that
enhanced the contrast shown in the final scans.

"For unknown reasons, the fMRI signals from the monkeys were
weaker than those from the humans," Orban said. "Since the
monkey brain is smaller, we needed to use a contrasting agent to
increase the fMRI's ability to pick up a signal."

While a regular MRI measures tissue density and structure, fMRI
measures the flow, volume and oxygenation of blood in tissue. In
the current study, this technique was used to investigate regions of
the brain that were activated when the subjects looked at the
moving 3-D images.

"The advantage of functional MRI is that scientists can see which
regions of the brain are active," Orban said.

The results showed pronounced differences between the two
species: in an area of the human visual cortex called V3A - an area
thought to be responsible for a variety of visual functions, such as
motion processing and stereoscopic depth - and also in the
intraparietal cortex. The researchers noted that, in humans, four
distinct areas of the intraparietal cortex were involved in processing
the rotating 3-D images. There is no clear counterpart to this
region in monkeys.

"The results suggest that, as humans evolved, some portions of
their brains adapted to produce specific abilities, such as
controlling fine motor skills," Orban said.

The results don't mean that monkeys don't have 3-D visual
capabilities. The findings do show that researchers now have a
technique enabling them to make reliable comparisons between a
monkey brain and a human brain.

"This study provides the first evidence of a functional difference
between the human and the monkey brain," Todd said. "The
results show that, in at least one important aspect, the brains
function quite differently."

"We were in a paradoxical situation before we had these results,"
Orban said. "On one hand, it's obvious that humans and monkeys
are different.

"On the other hand, when we use the physiology of the monkey
brain as a model to explain what we see in a human functional MRI
scan, we had assumed that the activity was occurring in the same
region in each brain. We had to make an assumption, which we
knew would be wrong from time to time. We just didn't know
when that assumption would be wrong."

"Now we have a way to verify when the monkey model does not
apply and when it really can apply," Orban said. "And we can be
much more precise in extrapolating findings from monkeys to
humans."

###

Support for this research came from the Inter-University Attraction
Poles (a Belgian research foundation); GOA (a regional research
support foundation in Belgium); the Fund for Scientific Research -
Flanders (FWO-Flanders); and the Queen Elisabeth Medical
Foundation.

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